A common nutrient found in protein-rich foods may play a bigger role in immune defense than scientists realized.
Researchers at The Rockefeller University have found that low levels of the amino acid arginine can make it harder for cells to display warning signals that help the immune system spot cancer and viral infections.
Their findings were published in the journal Cell.
Arginine is one of the amino acids the body uses to build proteins.
The body can make some arginine on its own, and people also obtain it from foods such as meat, fish, dairy products, nuts, seeds and legumes. Arginine is involved in many processes, including blood flow, healing and immune function.
Scientists have previously noticed unusually low arginine levels in several diseases. Colon cancer is one example. In earlier work published in 2023, the team led by cancer researcher Sohail Tavazoie found that depriving colon cancer cells of arginine caused them to develop more genetic mutations.
The new research asked a different question. Could a shortage of arginine also change the way the immune system recognizes dangerous cells? The answer appears to be yes, at least in laboratory and animal experiments.
The researchers focused on a protein called MHC-1. Almost every cell in the body carries MHC-1 proteins on its surface. These proteins work like display boards, showing small pieces of material from inside the cell to immune cells called T cells.
If a cell is infected by a virus, the display can contain pieces of viral proteins. Cancer cells can also produce abnormal proteins because of mutations. T cells can recognize some of these unusual signals and help destroy the affected cells.
First author Qiushuang Wu examined what happened when cells had less arginine available. The researchers found hundreds of proteins whose levels fell. Among the most important changes were reductions involving genes needed to make MHC-1.
The team discovered a surprisingly direct explanation. MHC-1 contains many places where arginine must be added while the protein is being built. When arginine became scarce, the cell’s protein-making machinery struggled to finish the job.
Proteins are assembled by tiny structures called ribosomes. Ribosomes read genetic instructions and connect amino acids in the correct order, rather like building an object from a detailed set of instructions. If an essential building material is missing, production can slow or stop.
That is what the researchers observed with MHC-1. Ribosomes stalled when they reached parts of the protein that required arginine. As a result, cells produced fewer complete MHC-1 proteins and displayed fewer immune warning signals on their surfaces.
This could give cancer cells or virus-infected cells an advantage. If fewer warning signals are visible, T cells may have more difficulty recognizing that something is wrong. The finding provides a possible link between poor nutrient availability and weaker immune surveillance.
The researchers studied several disease models, including colon cancer, influenza and COVID-19 caused by SARS-CoV-2. Arginine stood out because it was strongly depleted across these different conditions. This suggested that the effect might not be limited to one particular disease.
The team then tested whether changing dietary arginine could make a difference in mice. Animals eating a diet low in arginine developed more colon tumors. Mice receiving more arginine developed fewer tumors, suggesting that nutrient availability could influence the body’s ability to control cancer.
The viral infection experiments produced another interesting result. Mice fed more arginine experienced milder illness from influenza and SARS-CoV-2 models. Giving arginine after influenza infection also improved outcomes, according to the researchers.
The scientists found that a moderate increase in arginine could restore activity of genes involved in MHC-1 production. They suggested that the amount needed could be comparable to that found in a small number of commonly available arginine tablets. However, this does not mean people should begin taking supplements to prevent cancer or viral disease.
The evidence so far comes mainly from cells and animal models. Human bodies are much more complicated, and taking extra arginine may not produce the same effects in patients. Supplements can also interact with medicines or be unsuitable for people with certain medical conditions.
Still, the findings raise the possibility of testing arginine alongside existing treatments. One area of interest is cancer immunotherapy, which works by helping the immune system attack tumors. If low arginine weakens the signals needed for immune recognition, correcting that shortage might potentially make some immune treatments work better.
The research may also help explain why aging and poor nutrition can make people more vulnerable to disease. Arginine levels can decline with age, while illness itself can change how nutrients are used throughout the body. Lower arginine might therefore be one of several factors that weaken immune defenses in older or unwell people.
A major strength of the study is that it identifies a clear biological mechanism rather than simply showing an association. The researchers traced the problem from low arginine to stalled protein production and reduced MHC-1 signals, then tested dietary changes in animal models. That makes the findings more convincing as a starting point for further research.
The biggest limitation is that promising results in mice do not guarantee benefits in humans. It is also unclear what dose would be safe and useful, which patients might benefit, or whether tumors could respond differently depending on their biology. Carefully controlled clinical trials are needed before arginine can be recommended as part of cancer or infection treatment.
Overall, the study suggests that nutrition can influence immune defense in a remarkably direct way. Arginine is not simply fuel for the body; its availability may determine whether cells can build enough of an important protein used to alert immune cells.
If human studies confirm the effect, an inexpensive amino acid could eventually become a useful partner to more advanced therapies.
If you care about cancer, please read studies that a low-carb diet could increase overall cancer risk, and berry that can prevent cancer, diabetes, and obesity.
For more health information, please see recent studies about how drinking milk affects the risks of heart disease and cancer and results showing vitamin D supplements could strongly reduce cancer death.
Source: The Rockefeller University
